Prognostic Impact of Sinus Rhythm in Atrial Fibrillation Patients: Separating Rhythm Outcomes From Randomized Strategy Findings From the CABANA Trial.

Background: Clinically detected atrial fibrillation (AF) is associated with a significant increase in mortality and other adverse cardiovascular events. Since the advent of effective methods for AF rhythm control, investigators have attempted to determine how much these adverse prognostic AF effects could be mitigated by the restoration of sinus rhythm (SR) and whether the method used mattered.
Methods: The CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) randomized 2204 AF patients to ablation versus drug therapy, of which 1240 patients were monitored in follow-up using the CABANA ECG rhythm monitoring system. To assess the prognostic benefits of SR, we performed a prespecified analysis using Cox survival modeling with heart rhythm as a time-dependent variable and randomized treatment group as a stratification factor.
Results: In the 1240 patient study cohort, 883 (71.2%) had documented AF at some point during their postblanking follow-up. Among the 883 patients, 671 (76.0%) experienced AF within the first year of postblanking follow-up, and 212 (24.0%) experienced their first AF after ≥1 year of postblanking follow-up. The primary CABANA end point (death, disabling stroke, serious bleeding, or cardiac arrest) occurred in 95 (10.8%) of the 883 patients with documented AF and in 29 (8.1%) of the 357 patients with no AF recorded during follow-up. In multivariable time-dependent analysis, the presence of SR (compared with non-SR) was associated with a significantly reduced risk of the primary end point (adjusted hazard ratio, 0.57 [95% CI, 0.38-0.85]; P =0.006; independent of treatment strategy [ablation versus drugs]). Corresponding results for all-cause mortality were adjusted hazard ratio of 0.59 [95% CI, 0.35-1.01]; P =0.053).
Conclusions: In patients in the CABANA trial with detailed long-term rhythm follow-up, increased time in SR was associated with a clinically consequential decrease in mortality and other adverse prognostic events. The predictive value of SR was independent of the therapeutic approach responsible for reducing the burden of detectable AF.
Registration: URL: https://clinicaltrials.gov; Unique Identifier: NCT00911508.
Competing Interests: Disclosures Dr Packer reports grants from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), St. Jude Medical Corporation and Foundation, Biosense Webster Inc, Medtronic Corp, and Boston Scientific Corp during the conduct of the study; grants from Abbott, Biosense Webster Inc, Boston Scientific Corp, CardioFocus, Medtronic Inc, St. Jude Medical, CardioInsight, NIH, Siemens, Thermedical, Endosense, Robertson Foundation, and Hansen Medical; advisory board without compensation from Abbott, Biosense Webster Inc, Boston Scientific Corp, CardioFocus, Medtronic Inc, St. Jude Medical, Spectrum Dynamics, Siemens, Thermedical, Johnson & Johnson, and SigNum Preemptive Healthcare Inc; speaking with honorarium from Biotronik and MediaSphere Medical, LLC; and royalties from Wiley & Sons, Oxford, and St. Jude Medical. Dr Packer and Mayo Clinic jointly have equity in a privately held company, External Beam Ablation Medical Devices, outside the submitted work. In addition, Dr Packer has mapping technologies with royalties paid. Dr Piccini reports grants from ARCA Biopharma, Boston Scientific, Gilead Sciences, Janssen Pharmaceuticals, Abbott, and Verily; consulting from Allergan, Bayer, Johnson & Johnson, Medtronic, Sanofi, and Philips outside the submitted work. Dr Al-Khalidi reports grants from the NIH/NHLBI and Mayo Clinic during the conduct of the study. Dr Poole reports grants from ATriCure outside the submitted work. Dr Bahnson reports grants from the NIH/NHLBI and Mayo Clinic during the conduct of the study; grants from St. Jude Medical Inc, Abbott Medical, Biosense Webster Inc, Johnson & Johnson, NIH, and Boston Scientific, Corp; and consulting from Cardiofocus Inc, and Ventrix outside the submitted work. Dr Lee reports grants from the NIH/NHLBI and Mayo Clinic, as well as Data Safety Monitoring Board service on studies funded by AstraZeneca, Medtronic, Merck, Amgen, and the Cardiovascular Research Foundation during the conduct of the study. Dr Mark reports grants from NIH/NHLBI and Mayo Clinic during the conduct of the study; grants from Merck, Oxygen Therapeutics, Bristol Myers Squibb, AstraZeneca, University of Calgary, Eli Lilly & Company, AGA Medical, St. Jude Medical, and Tufts University; and personal fees from CeleCor outside the submitted work. The other authors report no conflicts.